Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

DNMT3A R882 mutations promote anthacyline resistance through impaired DNA-damage sensing

ABSTRACT: DNMT3A R882 mutations promote anthacyline resistance through impaired DNA-damage sensing

PROVIDER: PRJNA295441 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR2297230_1.fastq.gz	Fastqsanger.gz
	SRR2297230_2.fastq.gz	Fastqsanger.gz
	SRR2297231_1.fastq.gz	Fastqsanger.gz
	SRR2297231_2.fastq.gz	Fastqsanger.gz
	SRR2297232_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 42

Similar Datasets

DNMT3A R882 mutations promote anthacyline resistance through impaired DNA-damage sensing [Bisulfite-Seq]

Project description:Although the majority of acute myeloid leukemia (AML) patients initially respond to chemotherapy, most of them subsequently relapse due to persistent, chemoresistant disease. However, the mechanistic basis by which AML cells persist during chemotherapy has not been fully delineated. Recurrent somatic mutations in the DNA methyltransferase 3A gene (DNMT3A), most frequently at arginine 882 (DNMT3Amut), are commonly observed in AML patients, and are also detected in elderly subjects with clonal hematopoiesis in the absence of leukemic transformation. DNMT3Amut AML patients have an inferior outcome when treated with standard dose daunorubicin-based induction chemotherapy, suggesting that DNMT3Amut AML cells can persist following chemotherapy and drive relapse. DNMT3Amut cells show impaired nucleosome eviction and chromatin remodeling in response to DNA damage in the setting of anthracycline exposure. This defect leads to an inability to sense and repair DNA damage, which results in the accumulation of single-stranded DNA breaks and increased mutagenesis. Our studies identify a critical role for DNMT3A R882 mutations in driving AML chemoresistance, and highlight the importance of chromatin remodeling in the response to cytotoxic chemotherapy.

2016-11-14 | GSE86827 | GEO

DNMT3A R882 mutations promote anthacyline resistance through impaired DNA-damage sensing [ChIP-Seq]

2016-11-14 | GSE72882 | GEO

DNMT3A R882 mutations promote anthacyline resistance through impaired DNA-damage sensing [RNA-Seq]

2016-11-14 | GSE72737 | GEO

Structure-guided functional suppression of AML-associated DNMT3A hotspot mutations

Project description:DNA methyltransferases DNMT3A- and DNMT3B-mediated de novo DNA methylation critically regulates epigenomic and transcriptomic patterning during development. The hotspot DNMT3A mutations at the site of Arg822 (R882) promote macro-oligomer formation, leading to aberrant DNA methylation that in turn contributes to pathogenesis of acute myeloid leukemia (AML). However, the molecular basis underlying the hotspot mutation-induced functional mis-regulation of DNMT3A remains unclear. Here, we report the crystal structure of DNMT3A methyltransferase (MTase) domain, revealing a molecular basis for its DNMT3B-distinct oligomerization behavior. Introducing DNMT3B-converting mutations to DNMT3A R882 mutants also led to structure determination of R882H- and R882C-mutated DNMT3A, which show enhanced intermolecular contacts than wild-type DNMT3A. Consistently, our in vitro and genomic DNA methylation analyses reveal that the DNMT3B-converting mutations eliminate the gain-of-function effect of the DNMT3A R882 mutations in cells. Together, this study provides mechanistic insights into DNMT3A R882 mutation-triggered aberrant oligomerization and DNA hypomethylation in AML, with important implications in cancer therapy.

2023-12-31 | GSE225828 | GEO

Structure-guided functional suppression of AML-associated DNMT3A R882 mutations [methylation]

2023-12-31 | GSE226062 | GEO

Mus musculus

Project description:DNMT3A R882 mutations promote anthacyline resistance through impaired DNA-damage sensing [Bisulfite-Seq]

| PRJNA342651 | ENA

Mus musculus

Project description:DNMT3A R882 mutations promote anthacyline resistance through impaired DNA-damage sensing [ChIP-Seq]

| PRJNA295442 | ENA

Mus musculus

Project description:DNMT3A R882 mutations promote anthacyline resistance through impaired DNA-damage sensing [RNA-Seq]

| PRJNA295055 | ENA

DNMT3A R882 mutations promote anthacyline resistance through impaired DNA-damage sensing

Project description:This SuperSeries is composed of the SubSeries listed below.

2016-11-14 | GSE72883 | GEO

Single-cell multi-omics in human clonal hematopoiesis reveals that DNMT3A R882 mutations perturb early progenitor states through selective hypomethylation.

Project description:Clonal hematopoiesis (CH) reflects clonal expansion of blood stem and progenitor cells with somatic mutations. We leveraged multi-modality single-cell sequencing to capture mutation status together with the transcriptome and methylome of CD34+ hematopoietic progenitor cells from five individuals with DNMT3A R882-mutated CH.

2022-07-05 | GSE158067 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data